Estrogen Protects Lenses against Cataract Induced by Transforming Growth Factor-β (TGFβ)

Abstract

Cataract, already a major cause of visual impairment and blindness, is likely to become an increasing problem as the world population ages. In a previous study, we showed that transforming growth factor-β (TGFβ) induces rat lenses in culture to develop opacities and other changes that have many features of human subcapsular cataracts. Here we show that estrogen protects against cataract. Lenses from female rats are more resistant to TGFβ-induced cataract than those from males. Furthermore, lenses from ovariectomized females show increased sensitivity to the damaging effects of TGFβ and estrogen replacement in vivo, or exposure to estrogen in vitro, restores resistance. Sex-dependent and estrogen-related differences in susceptibility to cataract formation, consistent with a protective role for estrogen, have been noted in some epidemiological studies. The present study in the rat indicates that estrogen provides protection against cataract by countering the damaging effects of TGFβ. It also adds to an increasing body of evidence that hormone replacement therapy protects postmenopausal women against various diseases.

Hormone replacement therapy and cataract: a population-based case–control study

“…First, oestrogen receptor messenger RNA has been found in the human lens, suggesting that oestrogen has a direct effect on the lens. 30 In laboratory rat models, oestrogen has been found to protect against cataract induced by transforming growth factor-beta 6 and by methylnitrosourea. 7 Significantly, oestrogen has also been shown to have antioxidant properties.…”

“…5 In addition, evidence from laboratory studies has suggested that it may protect against the development of cataract. 6,7 Cataract is a major cause of poor vision and blindness, 8 with the worldwide prevalence estimated to increase from 16 million cases in 1997 to 40 million by the year 2020. 9 Any factor that reduces the incidence of cataract may thus be of great public health significance.…”

Rapid action of oestradiol against hydrogen peroxide-induced oxidative stress in cataractous lens epithelium: an in vitro study

“…1,18 The protective role of oestrogen in cataractogenesis has been well studied in in vivo and in vitro conditions. 5,6,12,15 This study elucidates the quick protective role of 17b-oestradiol against H 2 O 2 -induced oxidative stress in cultured LECs.…”

“…Oestrogen protects the lens against TGF-binduced cataract in the lens culture system. 5 Oestrogen has also been reported to exert protective effects in the rat model of age-related cataracts induced by methyl nitrosourea (MNU). 6 Oxidative stress is widely recognized as one of the major causes of cataract.…”

Increased Expression of Interleukin-18 in Lenses of Ovariectomized Rats

“…Previous studies have shown an increased prevalence of cataracts in postmenopausal women, and estrogen has been reported to be effective in preventing age-related cataracts. [5][6][7][8] Estrogen is a hormone that participates in regulating calcium (Ca) levels in the body, and postmenopausal women experience a drop in estrogen secretion. Bone resorption is regulated by estrogen, and a decrease in estrogen level leads to a decrease in vitamin D. Since vitamin D enhances Ca 2+ absorption from the small intestine, [9][10][11][12] postmenopausal women are at greater risk of osteoporosis and hypercalcemia/ hypocalcemia via the dysfunction in Ca 2+ regulation due to a chronic reduction in circulating estrogen levels.…”